Investigations will be conducted to determine the role that cyclic GMP may play in mediating the actions of biologically active substances that promote cellular events antagonistic to those which occur when the level of cellular cyclic AMP is elevated. The studies proposed include: defining the biologically active agents (i.e. including hormones and neurohormones) that promote cyclic GMP accumulation coincident with the alteration in a specific cellular function; determining the temperal relationship between the response elicited and the change induced in cellular cyclic GMP concentraion; defining the cellular component with which cyclic GMP interacts in mediating the cellular responses ascribed to it; and determining the characteristics of guanylate cyclase activity which provide for a greater rate of cyclic GMP generation upon interation with the cell of a substance that promotes increased cyclic GMP accumulation.